ABSTRACT
Unfolded-protein
response (UPR) denotes the upregulation of endoplasmic reticulum
(ER)-resident chaperone and foldase genes and numerous
other genes involved in secretory functions during the accumulation of
unfolded proteins into the ER. Overexpression of individual foldases
and chaperones has been used in attempts to improve protein production
in different production systems. We describe here a novel strategy to
improve foreign-protein production. We show that the constitutive
induction of the UPR pathway in Aspergillus niger var.
awamori can be achieved by expressing the activated form of
the transcription factor hacA. This induction enhances the
production of Trametes versicolor laccase by up to sevenfold
and of bovine preprochymosin by up to 2.8-fold in this biotechnically
important fungus. The regulatory range of UPR was studied by analyzing
the mRNA levels of novel A. niger var. awamori genes
involved in different secretory functions. This revealed both
similarities and differences to corresponding studies in
Saccharomyces
cerevisiae.
Improvement
of Foreign-Protein Production in Aspergillus niger var.
awamori by Constitutive Induction of the Unfolded-Protein
Response